Linked Life Data

16004930

Source:http://linkedlifedata.com/resource/pubmed/id/16004930

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-7-11
pubmed:abstractText
Monocrotaline is a representative naturally occurring genotoxic pyrrolizidine alkaloid. Metabolism of monocrotaline by liver microsomes of F344 female rats generated (+/-)6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) and monocrotaline-N-oxide as major metabolites. Metabolism in the presence of triacetyleandomycin, a P450 3A enzyme inhibitor, reduced the formation of DHP by 52% and monocrotaline N-oxide formation by 59%. Dexamethasone significantly induced microsomal monocrotaline metabolizing enzyme activities in rat liver and lung. Previously, we have identified a set of DHP-derived DNA adducts from DHP-modified calf thymus DNA by (32)P-post labeling/HPLC analysis. Metabolism of monocrotaline in the presence of calf thymus DNA resulted in a similar set of DHP-DNA adducts. These DHP-DNA adducts were also found in the liver DNA of rats treated with monocrotaline. The time course of the DHP-derived DNA adduct formation and removal in the liver of rats gavaged with a single dose (10mg/kg) of monocrotaline was similar to that of rats treated with riddelliine. The levels of DHP-DNA adducts in liver DNA of rats treated with monocrotaline were much lower than that of riddelliine-treated rats. Results from this study indicate that (i) DHP is a common reactive metabolite for retronecine-type of pyrrolizidine alkaloids, (ii) the formation of DHP-derived DNA adducts in the liver DNA of rats treated with monocrotaline suggests that monocrotaline-induced tumorigenicity is through a genotoxic mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Metabolic activation of the tumorigenic pyrrolizidine alkaloid, monocrotaline, leading to DNA adduct formation in vivo.
pubmed:affiliation
Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't